Current evidence for the risk of PR prolongation, QRS widening, QT prolongation, from lopinavir, ritonavir, atazanavir, and saquinavir: A systematic review.


Journal

Medicine
ISSN: 1536-5964
Titre abrégé: Medicine (Baltimore)
Pays: United States
ID NLM: 2985248R

Informations de publication

Date de publication:
06 Aug 2021
Historique:
received: 15 07 2020
accepted: 11 07 2021
entrez: 16 8 2021
pubmed: 17 8 2021
medline: 25 8 2021
Statut: ppublish

Résumé

Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir. In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies. We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment. Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.

Sections du résumé

BACKGROUND BACKGROUND
Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir.
METHODS METHODS
In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies.
RESULTS RESULTS
We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment.
CONCLUSION CONCLUSIONS
Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.

Identifiants

pubmed: 34397829
doi: 10.1097/MD.0000000000026787
pii: 00005792-202108060-00042
pmc: PMC8341216
doi:

Substances chimiques

Cytochrome P-450 CYP3A Inhibitors 0
Lopinavir 2494G1JF75
Atazanavir Sulfate 4MT4VIE29P
Saquinavir L3JE09KZ2F
Ritonavir O3J8G9O825

Types de publication

Journal Article Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

e26787

Informations de copyright

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

Déclaration de conflit d'intérêts

The authors have no funding and conflicts of interest to disclose.

Références

Driggin E, Madhavan MV, Bikdeli B, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol 2020;75:2352–71.
Asensio E, Acunzo R, Uribe W, Saad EB, Sáenz LC. Recommendations for the measurement of the QT interval during the use of drugs for COVID-19 infection treatment. Updatable in accordance with the availability of new evidence. J Interv Card Electrophysiol 2020;59:315–20.
Şimşek Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turk J Med Sci 2020;50(SI-1):611–9.
Yousefifard M, Zali A, Ali KM, et al. Antiviral therapy in management of COVID-19: a system- atic review on current evidence. Arch Acad Emerg Med 2020;8:01–9.
Hall DC, Ji H-F. A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease. Travel Med Infect Dis 2020;35:01–13.
Copertino DC Jr, Casado Lima BC, Duarte RR, et al. Antiretroviral drug activity and potential for pre-exposure prophylaxis against COVID-19 and HIV infection. J Biomol Struct Dyn 2021;11:01–4.
Michaud V, Dow P, Al Rihani SB, et al. Risk assessment of drug-induced long QT syndrome for some COVID-19 repurposed drugs. Clin Trans Sci 2021;14:20–8.
Hunt K, Hughes CA, Hills-Nieminen C. Protease inhibitor–associated QT interval prolongation. Ann Pharmacother 2011;45:1544–50.
Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane Database Syst Rev 2014;4:01–370.
Chinello P, Petrosillo N, Pittalis S, et al. QTc interval prolongation during favipiravir therapy in an Ebolavirus-infected patient. PLoS Negl Trop Dis 2017;11:01–6.
Carpenter A, Chambers OJ, El Harchi A, et al. COVID-19 management and arrhythmia: risks and challenges for clinicians treating patients affected by SARS-CoV-2. Front Cardiovasc Med 2020;7:01–5.
Crotti L, Arbelo E. COVID-19 treatments, QT interval and arrhythmic risk: the need for an international Registry on Arrhythmias. Heart Rhythm 2020;17:1423–4.
Liu J, Shah SK, Basu-Ray I, Garcia-Diaz J, Khalid K, Saeed M. QT prolongation in HIV-positive patients: Review article. Indian Heart J 2019;71:434–9.
Recanatini M, Poluzzi E, Masetti M, Cavalli A, De Ponti F. QT prolongation through hERG K+ channel blockade: current knowledge and strategies for the early prediction during drug development. Med Res Rev 2005;25:133–66.
Han S, Sun X, Zhang Z, Zhang L. The protease inhibitor atazanavir blocks hERG K+ channels expressed in HEK293 cells and obstructs hERG protein transport to cell membrane. Acta Pharmacol Sin 2015;36:454–62.
Anson B, Weaver J, Ackerman M, et al. Blockade of HERG channels by HIV protease inhibitors. Lancet 2005;365:682–6.
Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 2009;6:01–6.
Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:01–8.
Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons, 2nd ed.Chichester (UK):2019.
Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998;52:377–84.
Barwick MA, Bennett LM, Johnson SN, McGowan J, Moore JE. Training health and mental health professionals in motivational interviewing: a systematic review. Child Youth Serv Rev 2012;34:1786–95.
Busti A, Tsikouris J, Peeters M, et al. A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIV-positive patients. HIV Med 2006;7:317–22.
Sarapa N, Nickens DJ, Raber SR, Reynolds RR, Amantea MA. Ritonavir 100 mg does not cause QTc prolongation in healthy subjects: a possible role as CYP3A inhibitor in thorough QTc studies. Clin Pharmacol Ther 2008;83:153–9.
Byakika-Kibwika P, Lamorde M, Lwabi P, et al. Cardiac conduction safety during coadministration of artemether-lumefantrine and lopinavir/ritonavir in hiv-infected ugandan adults. Chemother Res Pract 2011;2011:01–4.
Vicente J, Zusterzeel R, Johannesen L, et al. Assessment of multi ion channel block in a phase i randomized study design: results of the Ci PA phase I ECG biomarker validation study. Clin Pharmacol Ther 2019;105:943–53.
Baker JR, Best AM, Pade PA, McCance-Katz EF. Effect of buprenorphine and antiretroviral agents on the QT interval in opioid-dependent patients. Ann Pharmacother 2006;40:392–6.
Rathbun CR, Liedtke MD, Blevins SM, et al. Electrocardiogram abnormalities with atazanavir and lopinavir/ritonavir. HIV Clin Trials 2009;10:328–36.
Zhang X, Jordan P, Cristea L, et al. Thorough QT/QTc study of ritonavir-boosted saquinavir following multiple-dose administration of therapeutic and supratherapeutic doses in healthy participants. J Clin Pharmacol 2012;52:520–9.
Boffito M, Jackson A, Pozniak A, et al. Effect of a modified saquinavir/ritonavir dosing regimen with lower dose lead-in phase on QTc interval, pharmacokinetics, antiviral activity and safety in treatment-Naïve HIV-1-infected patients. Drugs RD 2015;15:141–53.
Cao B, Wang Y, Wen D, et al. A Trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020;382:1787–99.
Peterson RL, Vock DM, Powers JH, et al. Analysis of an ordinal endpoint for use in evaluating treatments for severe influenza requiring hospitalization. Clin Trials 2017;14:264–76.
Food, Drug Administration, HHS. International conference on harmonisation; guidance on E14 clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs; availability. Notice Fed Regist 2005;70:61134–5.
Boettiger DC, Nguyen VK, Durier N, et al. Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: results from the TREAT Asia HIV Observational Database. J Acquir Immune Defic Syndr 2015;68:186–95.
World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach; 2013. Available at: http://www.ncbi.nlm.nih.gov/books/NBK195400/ . Accessed July 1, 2020.
Chandwani A, Shuter J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther Clin Risk Manag 2008;4:1023–33.
Achenbach CJ, Darin KM, Murphy RL, Katlama C. Atazanavir/ritonavir-based combination antiretroviral therapy for treatment of HIV-1 infection in adults. Future Virol 2011;6:157–77.
Cameron DW, Japour AJ, Xu Y, et al. Ritonavir and saquinavir combination therapy for the treatment of HIV infection. AIDS Lond Engl 1999;13:213–24.
Lv Z, Chu Y, Wang Y. HIV protease inhibitors: a review of molecular selectivity and toxicity. HIVAIDS Auckl NZ 2015;7:95–104.

Auteurs

Denio A Ridjab (DA)

School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH